The abnormal pattern of visual evoked potentials in rabbits with hepatic encephalopathy (HE) due to fulminant hepatic failure (FHF) resembles that induced by barbiturates and benzodiazepines. As these drugs induce neural inhibition by interacting with receptors for the inhibitory neurotransmitter Gamma-aminobutyric acid (GABA) on postsynaptic neural membranes, this finding implies that neuronal activity in HE is similar to that induced by GABA. Outside the CNS the main source GABA is gut bacteria and the main site of its catabolism is the liver. When FHF was induced in rabbits the onset of HE was preceded by a marked increase in the plasma levels of GABA-like activity and by an increase in the permeability of the blood brain barrier (BBB). FHF was associated with a twofold increase in the number of GABA receptors and a decrease in the number of receptors for the excitatory neurotransmitter glutamate on postsynaptic membranes. In FHF there is an increase in the content of cholesterol and phospholipid relative to that of protein in brain synaptic membranes. These findings suggest that as the liver fails: 1) impaired hepatic metabolism of GABA leads to an increase of gut-derived GABA in plasma and 2) plasma GABA gains access to the brain through a permeable BBB and induces neural inhibition. Changes in the composition of neural membranes and neurotransmitter receptors in liver failure may render the brain less sensitive to excitatory neurotransmitter and more sensitive to inhibitory neurotransmitters.